Barriers to new drug development in respiratory disease

G Protein–Coupled Receptors in Asthma Therapy: Pharmacology and Drug Action

“…The results predicted a ligandbinding mode in which the ligand formed extensive interactions with the extracellular regions of TM4, TM5, TM7, as well as ECL2. Although current therapeutic methods including the combined use of ICS with LABAs are highly effective in most asthma patients, there is still a need for developing new therapies (Adcock et al, 2008;Barnes, 2010b;Brigden et al, 2016;Fajt and Wenzel, 2017;Gross and Barnes, 2017;Zhu et al, 2018). There are a number of proinflammatory mediators, including PGs, leukotrienes, and chemokines, which play important roles in the pathogenesis of asthma and bind GPCRs.…”

Neutrophil-targeted, protease-activated pulmonary drug delivery blocks airway and systemic inflammation

“…Pulmonary drug delivery offers an alternative route for direct administration of therapeutics to airway PMNs, with the added potential to reduce the overall dose needed and reduce possible systemic toxicity. One challenge to the pulmonary delivery of nonencapsulated drugs is the highly proteolytic microenvironment in pathological areas, which can severely reduce their efficacy (12)(13)(14). The hydrophobic nature of Pulmonary drug delivery presents a unique opportunity to target lower airway inflammation, which is often characterized by the massive recruitment of neutrophils from blood.…”